Prospero‐related homeobox 1 drives angiogenesis of hepatocellular carcinoma through selectively activating interleukin‐8 expression

Liu, Yanfeng; Zhang, Yonglong; Wang, Shenghao; Dong, Qiongzhu; Shen, Zhongliang; Wang, Wei; Tao, Shuai; Gu, Cheng; Liu, Jing; Xie, Youhua; Qin, Lun–Xiu

doi:10.1002/hep.29337

Cited by 33 publications

(28 citation statements)

References 36 publications

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“…In HCC, USP7 was highly expressed in cancer tissues [15]. USP7 could inhibit the ubiquitination of P65 and stabilize the expression of P65, thereby promoting the progress of hepatoma cancer [16]. In addition, reported data supports that USP7 can be used as a new independent prognostic factor for liver cancer [17].…”

Section: Introductionmentioning

confidence: 67%

Ubiquitin-specific protease 7 is a drug-able target that promotes hepatocellular carcinoma and chemoresistance

Zhang

et al. 2020

Cancer Cell Int

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Background: Ubiquitin-specific protease 7 (USP7) is a de-ubiquitin enzyme that plays an essential role in multiple cancers and becomes a target for treatment. However, the role of USP7 and its therapeutic value for HCC remains unclear. Methods: USP7 expression was examined in HCC tissues by western blot and immunohistochemistry. The correlation of USP7 and HCC prognosis was analyzed by Kaplan-Meier survival method. Mass spectrometry was determined and cell proliferation and tumorigenicity assays were conducted in vitro and in vivo treated by P22077 and sgRNA-USP7. Results: USP7 expression was significantly increased in HCC and associated with its progression. Interestingly, many HCC cells are sensitive to USP7 inhibition by using P22077. P22077 treatment not only induced cell death but also inhibited cell proliferation and migration in Huh7 and SK-Hep1 cells. In a xenograft model, P22077 efficiently inhibited tumor growth. In chemo-resistant HCC cells, P22077 decreased cell sensitivity to chemotherapy. In addition, mass spectrometry reveals 224 of significantly changed proteins upon P22077 treatment. Conclusions: We demonstrate a critical role of USP7 in HCC devolvement and chemoresistance. Disruption of USP7 function results in dis-regulated several key biological processes and subsequently activates BAX. USP7 might be a novel and drug-able target in HCC.

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Section: Introductionmentioning

confidence: 67%

Ubiquitin-specific protease 7 is a drug-able target that promotes hepatocellular carcinoma and chemoresistance

Zhang

et al. 2020

Cancer Cell Int

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“…WWOX, a gene bearing the WW domain, straddles a very common chromosomal fragile site (FRA16D) which is known to be altered in various types of cancers . Addressing the vital role of angiogenesis is important in the process of tumorigenesis and the metastasis or recurrence in HCC . Previous studies showed that low WWOX expression may aid in the promotion of angiogenesis in various cancers, and also showed that the methylation of WWOX gene promoter CpG island was associated with suppression of WWOX expression .…”

Section: Discussionmentioning

confidence: 99%

Low expression of WW domain‐containing oxidoreductase associates with hepatocellular carcinoma aggressiveness and recurrence after curative resection

et al. 2018

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WW domain‐containing oxidoreductase (WWOX), which has a protein‐interaction domain and is regarded to be a tumor suppressor, has been known to play an important role in anti‐angiogenesis and cancer progression. This study aimed to investigate prognostic values of WWOX expression in hepatocellular carcinoma (HCC) patients after hepatectomy. Additionally, we intended to formulate a valuable prognostic nomogram for HCCs. 182 HCC patients who underwent hepatectomy from January 2009 to January 2010 were enrolled in our study. qRT‐PCR, Western blot, and immunohistochemistry on tissue microarrays were then used to determine the expression levels of WWOX. An evaluation of the role of WWOX expression levels in the prognosis and outcome of patients was established. A decrease in the expression of WWOX was found when compared to adjacent tumor‐free tissues, which led to worse overall survival (OS) and recurrence‐free survival (RFS) and, therefore, was considered as an independent negative factor in the prognosis of HCC. Two nomograms, comprising WWOX, alpha‐fetoprotein (AFP), tumor size, and γ‐glutamyltransferase (γ‐GT), were constructed to obtain superior discriminatory abilities than conventional staging systems in terms of C‐index and clinical net benefit on decision curve analysis (DCA) for OS and RFS. Our data suggest that WWOX expression is strongly related to HCC post‐resection aggressiveness and recurrence. Additional advanced and accurate predictive model through the incorporation of WWOX into nomogram could help predict OS or RFS for HCC patients.

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“…PROX1 is a nuclear transcription factor associated with the embryonic development of multiple organs, including the central nervous system, heart, lymphatic system, skeletal muscles, lens, retina, and so on [102]. Reportedly, PROX1 plays various tumor-dependent functional roles, which reflect both the oncogenic potential and a tumor-suppressive role [90].…”

Section: Novel Prognosticators Of Osccmentioning

confidence: 99%

“…Reportedly, PROX1 plays various tumor-dependent functional roles, which reflect both the oncogenic potential and a tumor-suppressive role [90]. In addition, PROX1 promoted cell growth, angiogenesis, and sorafenib resistance in patients with HCC [102,91] and is associated with the lymphangiogenesis, metastasis, and poor prognosis in various malignancies [92,103,104]. However, high PROX1 expression is related to better prognosis for pancreatic and gastric cancer patients [105,106].…”

Section: Novel Prognosticators Of Osccmentioning

confidence: 99%

Hallmarks of Cancer-Related Newly Prognostic Factors of Oral Squamous Cell Carcinoma

Sasahira

Kirita

2018

IJMS

206

184

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Head and neck cancer, including oral squamous cell carcinoma (OSCC), is the sixth leading malignancy worldwide. OSCC is an aggressive tumor and its prognosis has exhibited little improvement in the last three decades. Comprehensive elucidation of OSCC’s molecular mechanism is imperative for early detection and treatment, improving patient survival. Based on broadly accepted notions, OSCC arises from multiple genetic alterations caused by chronic exposure to carcinogens. In 2011, research revealed 10 key alterations fundamental to cancer cell development: sustaining proliferative signaling, evading growth suppressors, avoiding immune destruction, activating invasion and metastasis, tumor-promoting inflammation, enabling replicative immortality, inducing angiogenesis, genome instability and mutation, resisting cell death, and deregulating energetics. This review describes molecular pathological findings on conventional and novel hallmarks of OSCC prognostic factors. In addition, the review summarizes the functions and roles of several molecules as novel OSCC prognosticators.

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Prospero‐related homeobox 1 drives angiogenesis of hepatocellular carcinoma through selectively activating interleukin‐8 expression

Abstract: We have identified PROX1 as a crucial promoter of HCC angiogenesis; our study provides an insight into PROX1's function in HCC progression and the potential therapeutic application of anti-IL-8 antibody in high PROX1 expression HCC patients. (Hepatology 2017;66:1894-1909).

Cited by 33 publications

References 36 publications

Ubiquitin-specific protease 7 is a drug-able target that promotes hepatocellular carcinoma and chemoresistance

Ubiquitin-specific protease 7 is a drug-able target that promotes hepatocellular carcinoma and chemoresistance

Low expression of WW domain‐containing oxidoreductase associates with hepatocellular carcinoma aggressiveness and recurrence after curative resection

Hallmarks of Cancer-Related Newly Prognostic Factors of Oral Squamous Cell Carcinoma

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